Barui, S. | Search bioRxiv

bioRxiv2020

A study of conventional histological parameters in excision specimens of breast cancer over a 7 year period and association with immunohistochemical categories

Background Along with conventional histological examination, immunohistochemistry (IHC) is a useful adjunct to assessment of a breast cancer excision specimen. Previous studies have shown differences in behavior of neoplasms depending on their histopathological as well as immunohistochemical categories; in particular, triple negative breast cancers (on IHC) show the worst prognosis.Objectives To find association, if any, within conventional histopathological characteristics (size, grade, stage, mitotic count, desmoplasia, dense inflammatory infiltrate, lymphovascular invasion) and between the conventional parameters and immunohistochemical categories of breast cancer, in both primary and post neo adjuvant chemotherapy (NACT) specimens.Methods 177 breast cancer excision specimens examined over last 7 years were assessed retrospectively, their histopathological parameters were recorded. In cases where immunohistochemistry was performed (N=108) the specimen was placed in one of the immunohistochemical categories: Luminal A, Luminal B, Her2 and Triple negative cancers. The data was then analysed by standard statistical methods.Results No statistically significant association was found between the histopathological parameters and IHC category was. However, a strong correlation was seen between lymphovascular invasion within the primary tumor and increasing lymph node involvement. There was also a reduction in ER and PR expression in neoplasms post NACT, while HER2 expression remained largely unchanged.Conclusion There might be additional genetic subtypes underlying the immunohistochemical phenotypes which determine the morphological characteristics of the neoplasm.Competing Interest StatementThe authors have declared no competing interest.View Full Text

pathology↗

bioRxiv2019

Paradoxical role of AT-rich interactive domain 1A in restraining pancreatic carcinogenesis

Background & AimsARID1A is postulated to be a tumor suppressor gene owing to loss-of-function mutations in human pancreatic ductal adenocarcinomas (PDAC). However, its role in pancreatic pathogenesis is not clear despite recent studies using genetically engineered mouse (GEM) models. We aimed at further understanding of its direct functional role in PDAC, using a combination of GEM model, PDAC cell lines. MethodsPancreas-specific mutant Arid1a-driven GEM model (Ptf1a-Cre;KrasG12D;Arid1af/f or "KAC") was generated by crossing Ptf1a-Cre;KrasG12D ("KC") mice with Arid1af/f mice and characterized histologically with timed necropsies. Arid1a was also deleted using CRISPR-Cas9 system in established PDAC cell lines to study the immediate effects of Arid1a loss in isogenic models. Cells lines with or without Arid1a expression were developed from respective autochthonous PDAC GEM models, compared functionally using various culture assays, and subjected to RNA-sequencing for comparative gene expression analysis. DNA damage repair was analyzed in cultured cells using immunofluorescence and COMET assay. ResultsArid1a is critical for early progression of mutant Kras-driven pre-malignant lesions into PDAC, as evident by lower Ki-67 and higher apoptosis staining in "KAC" as compared to "KC" mice. Enforced deletion of Arid1a in established PDAC cell lines caused suppression of cellular growth and migration, accompanied by compromised DNA damage repair. Despite early development of relatively indolent cystic precursor lesions called intraductal papillary mucinous neoplasms (IPMNs), a subset of "KAC" mice developed aggressive PDAC in later ages. PDAC cells obtained from older autochthonous "KAC" mice revealed epigenetic changes underlying the various compensatory mechanisms to overcome the growth suppressive effects of Arid1a loss. ConclusionsArid1a is an essential survival gene whose loss impairs cellular growth, and thus, its expression is critical during early stages of pancreatic tumorigenesis in mouse models.

cancer biology↗